Biomaterials are designed to replace injured or diseased tissue. Ideally, they are scaffolds for tissue regeneration with properties similar to those of the healthy tissue that they replace. Designed to cover a two-dimensional surface or to fill a three-dimensional void, they should, in parallel to healing, gradually be absorbed so that, ultimately, the site of injury becomes almost indistinguishable from the surrounding tissue. To achieve these goals, the biomaterial must fulfil several design requirements: it has to possess a sufficiently large porosity, its surface chemistry and topography must be suited for cell adhesion, proliferation and differentiation; it needs to possess an appropriate architecture to guide tissue regeneration; and it should allow for controlled absorption when the scaffold is no longer required. Additionally, the scaffold must, despite a high overall porosity that considerably weakens its mechanical properties, possess sufficient stiffness, strength and toughness to perform the natural tissue's function while the wound is healing. The currently available tissue scaffolds comprise different unabsorbable biocompatible polymers such as polyethylene terephthalate; fluorinated polymers, such as polytetrafluoroethylene (PTFE) and fibres of expanded PTFE; and polyurethanes. Some available tissue scaffolds do comprise absorbable polymers such as poly-lactic acid, hyaluronic acid, collagen and gelatin. However, their pore geometry ranges are not optimal.
Typical methods for preparing such three-dimensional porous polymer scaffolds include: a solvent-casting and particle-leaching technique comprising mixing a polymer with single-crystal salt particles, drying the mixture and then immersing the dried material to leach the salt particles (A. G. Mikos et al., Polymer, 35, 1068 (1994)); a gas forming technique comprising expanding a polymer with CO2 gas (L. D. Harris et al., J. Biomed. Mater. Res., 42, 396 (1998)); a thermally induced phase separation technique including immersing a polymer-containing solvent in a non-solvent to make the polymer porous (C. Schugens, et al., J. Biomed. Mater. Res., 30, 449 (1996)); and a freeze-drying method comprising dissolving a polymer in a solvent to prepare a polymer solution and then freeze-drying the polymer solution with liquid nitrogen (K. Whang, Polymer, 36, 837 (1995). A specialized form of thermal induced phase separation, also referred to as directional freeze casting, has obtained the most defined porous tissue scaffolds thus far and is extensively described in the literature (Wegst et al Phil. Trans. R. Soc. A 2010, 368 p. 2099-2122). This method depends on the controlled solidification of a solvent, such as water, in a dispersion which results in the directional phase separation between solvent and the dispersed material due to directional growth of solid solvent crystals. After removal of the solvent (e.g. freeze-drying) a porous material remains. This method allows some control of the geometry of the material by controlling the speed at which the freeze front travels through the dispersed material. The tissue scaffold materials Remaix and OptiMaix comprising animal derived natural collagen and elastin are prepared using a freeze casting method, which is described in U.S. Pat. No. 6,447,701.
However, for many applications it is preferable that the material be highly uniform (e.g. the material density, pore size and pore orientation or mechanical properties should be have a limited variation throughout the material). The current biocompatible polymer porous tissue scaffolds lack sufficient uniformity. In addition, preferred custom-made biocompatible polymers with enhanced properties for cell attachment and growth are designed to be completely and molecularly soluble in an aqueous solvent or solvent mixture. Furthermore, it is usually desirable that these biocompatible polymers be highly purified and freed from soluble and insoluble (particulate) impurities. The use of such a molecularly dissolved biocompatible polymer improves the homogeneity of the resulting porous scaffold. The object of the current invention is to provide a process by which highly uniform biocompatible polymer tissue scaffolds, comprising biocompatible polymers, and articles prepared with these tissue scaffolds may be prepared.